This research involves detailed studies of the fibrinolytic antiactivator in plasma. This inhibitor of activation will be isolated, purified and subjects to physico-chemical characterization. Kinetic studies will be performed both in purified systems and in plasma. The binding and dissociation of the activator-antiactivator complex will be determined using as activator the plasma activator, the proactivator-streptokinase complex and urokinase. Binding between the activators and the antiactivator is effectively blocked by compounds, such as the substituted benzoates in relatively low concentrations. A search for other non-toxic, effective blocking agents will be performed. Attempts will be made to locate the active sites on the activators and the portions of the molecules involved in the interaction between activators and antiactivators. The mechanism through which the blocking agents prevent binding between activator and antiactivator will be explored. When the basic in vitro studies have been completed, in vivo tests of the effectiveness of the blocking agents and the degree of fibrinolytic activation, both with and without administered exogenous activators, will be performed. In these studies animal models will be used.